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Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic Fibrosis‐Related Pseudomonas aeruginosa Biofilms
Author(s) -
Thorn Chelsea R.,
CarvalhoWodarz Cristiane de Souza,
Horstmann Justus C.,
Lehr ClausMichael,
Prestidge Clive A.,
Thomas Nicky
Publication year - 2021
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.202100531
Subject(s) - biofilm , tobramycin , pseudomonas aeruginosa , cystic fibrosis , microbiology and biotechnology , antibiotics , ciprofloxacin , penetration (warfare) , chemistry , bacteria , medicine , biology , gentamicin , genetics , operations research , engineering
Pseudomonas aeruginosa biofilms cause persistent and chronic infections, most known clinically in cystic fibrosis (CF). Tobramycin (TOB) is a standard anti‐pseudomonal antibiotic; however, in biofilm infections, its efficacy severely decreases due to limited permeability across the biofilm matrix. Herewith, a biomimetic, nanostructured, lipid liquid crystal nanoparticle‐(LCNP)‐formulation is discovered to significantly enhance the efficacy of TOB and eradicate P. aeruginosa biofilm infections. Using an advanced, biologically‐relevant co‐culture model of human CF bronchial epithelial cells infected with P. aeruginosa biofilms at an air–liquid interface, nebulized TOB‐LCNPs completely eradicated 1 × 10 9 CFU mL −1 of P. aeruginosa after two doses, a 100‐fold improvement over the unformulated antibiotic. The enhanced activity of TOB is not observed with a liposomal formulation of TOB or with ciprofloxacin, an antibiotic that readily penetrates biofilms. It is demonstrated that the unique nanostructure of the LCNPs drives the enhanced penetration of TOB across the biofilm barrier, but not through the healthy lung epithelium barrier, significantly increasing the available antibiotic concentration at the site of infection. The LCNPs are an innovative strategy to improve the performance of TOB as a directed pulmonary therapy, enabling the administration of lower doses, reducing the toxicity, and amplifying the anti‐biofilm activity of the anti‐pseudomonal antibiotic.